The specific aims of the proposed experiments are: 1) To determine how NAC1 over expression in the nucleus accumbens (NAc) of rats affects the acquisition, maintenance, and reinstatement of cocaine self- administration. 2) To determine how self-administration of cocaine affects NAc protein levels and localization of the 20S proteasome, the E3 ligase Cul3, and poly-ubiquitinated proteins as well as the activity of the proteasome. 3) To determine how the loss of the NAC1 gene in knockout mice affects cocaine self- administration, the protein levels and localization of the above proteins, and proteasome activity. Experiments will use self-administration as the model of addiction and rats will receive AAV-NAC1 infusions to investigate over expression. The NAc from rats and mice will be dissected and sub fractionated to retrieve the cytosolic, nuclear, and postsynaptic density fractions. Some fractions will then undergo proteasome activity assays. Other fractions will undergo immunoblotting to determine fraction levels of the 20S subunit, Cul3, and poly-ubiquitinated proteins. Together, these findings will provide important new information regarding the neuroplastic changes induced by cocaine addiction. [unreadable] [unreadable] [unreadable]